Investigations will be undertaken to define the role of presynaptic regulation of norepinephrine release in vitro in a densely innervated muscular artery in normotensive rats. Physiological stress (swimming and/or temperature adaptation) will be used to produce elevated or depressed levels of neurogenic vasoconstrictor tone the level of which will be quantified by measuring enzymatic activities in the blood vessel (tyrosine hydroxylase) and/or sympathetic ganglia (choline acetyltransferase). Assessment of the presynaptic regulatory actions of norepinephrine, isoproterenol and angiotensin II after chronic but physiologic elevations or depression of sympathetic vasomotor nerve activity will allow a quantitative relationship between nerve activity and presynaptic regulatory mechanism to be idnetified and defined (e.g. sub- or super sensitivity). Using this background information, rats with experimental hypertension (neurogenic, SHR, renal or DOCA-Na) and sham normotensives will be investigated to determine whether these presynaptic regulatory mechanism are altered in the hypertensive state. After superimposing physiological stress to alter sympathetic nerve activity upon these hypertensive states the presynaptic regulatory function will be reassessed in the isolated artery preparation and compared to that in normotension to ascertain whether the adaptation of these systems may be exaggerated or minimized by the presence of a hypertensive condition. Investigations will be undertaken to assess limited aspects of presynaptic regulation of norepinephrine release in intact vascular beds. This will include study of the adaptive responses of these presynaptic regulatory mechanism in both normo- and hypertension thereby contributing to our understanding of the pathogenesis of essential hypertension.